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"Sharmila, S."
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Tryptophan Metabolism by Gut Microbiome and Gut-Brain-Axis: An in silico Analysis
2019
The link between gut microbiome and brain is being slowly acknowledged due to the speculated role of resident gut microbial community in altering the functions of gut-brain axis (GBA). Recently, a number of microbial metabolites (referred to as neuro-active metabolites) produced through tryptophan metabolism have been suggested to influence the GBA. In view of this, the current study focuses on microbial tryptophan metabolism pathways which produce neuro-active metabolites. An
analysis was performed on bacterial genomes as well as publicly available gut microbiome data. The results provide a comprehensive catalog of the analyzed pathways across bacteria. The analysis indicates an enrichment of tryptophan metabolism pathways in five gut-associated phyla, namely, Actinobacteria, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria. Further, five genera, namely,
,
,
,
, and
have been predicted to be enriched in terms of number of the analyzed tryptophan metabolism pathways, suggesting a higher potential of these bacterial groups to metabolize tryptophan in gut. Analysis of available microbiome data corresponding to gut samples from patients of neurological diseases and healthy individuals suggests probable association of different sets of tryptophan metabolizing bacterial pathways with the etiology of different diseases. The insights obtained from the present study are expected to provide directions toward designing of microbiome based diagnostic and therapeutic approaches for neurological diseases/disorders.
Journal Article
Host-microbiome interactions: Gut-Liver axis and its connection with other organs
2022
An understanding of connections between gut microbiome and liver has provided important insights into the pathophysiology of liver diseases. Since gut microbial dysbiosis increases gut permeability, the metabolites biosynthesized by them can reach the liver through portal circulation and affect hepatic immunity and inflammation. The immune cells activated by these metabolites can also reach liver through lymphatic circulation. Liver influences immunity and metabolism in multiple organs in the body, including gut. It releases bile acids and other metabolites into biliary tract from where they enter the systemic circulation. In this review, the bidirectional communication between the gut and the liver and the molecular cross talk between the host and the microbiome has been discussed. This review also provides details into the intricate level of communication and the role of microbiome in Gut-Liver-Brain, Gut-Liver-Kidney, Gut-Liver-Lung, and Gut-Liver-Heart axes. These observations indicate a complex network of interactions between host organs influenced by gut microbiome.
Journal Article
Recent poleward shift of tropical cyclone formation linked to Hadley cell expansion
2018
Recent research indicates that the annual-mean locations of tropical cyclones have migrated toward higher latitudes. Concurrently, an anthropogenically forced tropical expansion has been observed, yet the connection between the two processes remains little-explored. Here, using observational and reanalysis data, we investigate how large-scale dynamical effects, combined with coherent changes in the regional Hadley circulation, explain recent changes in regional tropical cyclone genesis over 1980–2014. We show that the recent anomalous upper-level weakening of the rising branch of the Hadley circulation in the deep tropics, possibly induced by the increased vertical stability, has likely suppressed the low-latitude tropical cyclone genesis in most ocean basins via anomalous large-scale subsidence. Regional Hadley circulation variations have also favoured a poleward displacement of tropical-cyclone-favourable climate conditions through poleward shift of the Hadley circulation’s meridional extent. With projections indicating continued tropical expansion, these results indicate that tropical cyclone genesis will also continue to shift poleward, potentially increasing tropical-cyclone-related hazards in higher-latitude regions.
Journal Article
‘NetShift’: a methodology for understanding ‘driver microbes’ from healthy and disease microbiome datasets
by
Chandrakar, Pranjal
,
Mande, Sharmila S.
,
Kuntal, Bhusan K.
in
631/158/2451
,
631/326/2565/855
,
Biomedical and Life Sciences
2019
The combined effect of mutual association within the co-inhabiting microbes in human body is known to play a major role in determining health status of individuals. The differential taxonomic abundance between healthy and disease are often used to identify microbial markers. However, in order to make a microbial community based inference, it is important not only to consider microbial abundances, but also to quantify the changes observed among inter microbial associations. In the present study, we introduce a method called ‘NetShift’ to quantify rewiring and community changes in microbial association networks between healthy and disease. Additionally, we devise a score to identify important microbial taxa which serve as ‘drivers’ from the healthy to disease. We demonstrate the validity of our score on a number of scenarios and apply our methodology on two real world metagenomic datasets. The ‘NetShift’ methodology is also implemented as a web-based application available at
https://web.rniapps.net/netshift
Journal Article
Mechanisms of multiyear variations of Northern Australia wet-season rainfall
2020
Northern Australia wet season (November–April) rainfall exhibits strong variability on multiyear timescales. In order to reveal the underlying mechanisms of this variability, we investigate observational records for the period 1900–2017. At multiyear timescales, the rainfall varies coherently across north-western Australia (NW) and north-eastern Australia (NE), but the variability in these two regions is largely independent. The variability in the NE appears to be primarily controlled by the remote influence of low frequency variations of El Niño-Southern Oscillation (ENSO). In contrast, multiyear variations in the NW appear to be largely driven locally and stem from a combination of rainfall-wind-evaporation feedback, whereby enhanced land-based rainfall is associated with westerly wind anomalies to the west that enhance local evaporation over the ocean to feed the enhanced land based rainfall, and soil moisture-rainfall feedback. Soil-moisture and associated evapotranspiration over northern Australia appear to act as sources of memory for sustaining multiyear wet and dry conditions in the NW. Our results imply that predictability of multiyear rainfall variations over the NW may derive from the initial soil moisture state and its memory, while predictability in the NE will be limited by the predictability of the low frequency variations of ENSO.
Journal Article
Global Profiling of Carbohydrate Active Enzymes in Human Gut Microbiome
by
Mande, Sharmila S.
,
Bhattacharya, Tanudeep
,
Ghosh, Tarini Shankar
in
Adult
,
Age Factors
,
Analysis
2015
Carbohydrate Active enzyme (CAZyme) families, encoded by human gut microflora, play a crucial role in breakdown of complex dietary carbohydrates into components that can be absorbed by our intestinal epithelium. Since nutritional wellbeing of an individual is dependent on the nutrient harvesting capability of the gut microbiome, it is important to understand how CAZyme repertoire in the gut is influenced by factors like age, geography and food habits.
This study reports a comprehensive in-silico analysis of CAZyme profiles in the gut microbiomes of 448 individuals belonging to different geographies, using similarity searches of the corresponding gut metagenomic contigs against the carbohydrate active enzymes database. The study identifies a core group of 89 CAZyme families that are present across 85% of the gut microbiomes. The study detects several geography/age-specific trends in gut CAZyme repertoires of the individuals. Notably, a group of CAZymes having a positive correlation with BMI has been identified. Further this group of BMI-associated CAZymes is observed to be specifically abundant in the Firmicutes phyla. One of the major findings from this study is identification of three distinct groups of individuals, referred to as 'CAZotypes', having similar CAZyme profiles. Distinct taxonomic drivers for these CAZotypes as well as the probable dietary basis for such trends have also been elucidated. The results of this study provide a global view of CAZyme profiles across individuals of various geographies and age-groups. These results reiterate the need of a more precise understanding of the role of carbohydrate active enzymes in human nutrition.
Journal Article
In vitro and in silico studies of silver nanoparticles (AgNPs) from Allium sativum against diabetes
2022
In the present study, the silver nanoparticles (AgNPs) were synthesized from the bulbs of
Allium sativum
, characterized by UV–visible spectroscopy, FT-IR, SEM, HR-TEM, EDAX analysis and investigated its action on the inhibition of starch digestion. The results proved that the biosynthesized nanoparticles were uniformly dispersed, spherical shaped with the size ranging from 10 to 30 nm. The phytochemical and FT-IR analysis showed the presence of phenols, terpenoids, and amino acids in the synthesized AgNPs. The cytotoxicity analysis revealed that the synthesized AgNPs were non-toxic to the normal cells. The synthesized AgNPs exhibited significant free radical scavenging activity. The in vitro antidiabetic activity showed that the synthesized AgNPs increased glucose utilization, decreased hepatic glucose production, inhibited the activity of starch digestive enzymes such as α-amylase and α-glucosidase, and were not involved in the stimulation of pancreatic cells for the secretion of insulin. The in silico antidiabetic activity analysis (molecular docking) also revealed that the silver atoms of the AgNPs interacted with the amino acid residues of α-amylase, α-glucosidase, and insulin. The present study proved that the AgNPs synthesized from
A. sativum
have prominent antidiabetic activity in terms of reducing the hyperglycemia through the increased glucose utilization, decreased hepatic glucose production, and the inhibition of α-amylase and α-glucosidase enzymes. So it can be used as a promising nanomedicine for the treatment of diabetes.
Journal Article
Xenobiotic Metabolism and Gut Microbiomes
2016
Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends.
Journal Article
Identification and Functional Characterization of Gene Components of Type VI Secretion System in Bacterial Genomes
2008
A new secretion system, called the Type VI Secretion system (T6SS), was recently reported in Vibrio cholerae, Pseudomonas aeruginosa and Burkholderia mallei. A total of 18 genes have been identified to be belonging to this secretion system in V. cholerae. Here we attempt to identify presence of T6SS in other bacterial genomes. This includes identification of orthologous sequences, conserved motifs, domains, families, 3D folds, genomic islands containing T6SS components, phylogenetic profiles and protein-protein association of these components. Our analysis indicates presence of T6SS in 42 bacteria and its absence in most of their non-pathogenic species, suggesting the role of T6SS in imparting pathogenicity to an organism. Analysis of genomic regions containing T6SS components, phylogenetic profiles and protein-protein association of T6SS components indicate few additional genes which could be involved in this secretion system. Based on our studies, functional annotations were assigned to most of the components. Except one of the genes, we could group all the other genes of T6SS into those belonging to the puncturing device, and those located in the outer membrane, transmembrane and inner membrane. Based on our analysis, we have proposed a model of T6SS and have compared the same with the other bacterial secretion systems.
Journal Article
A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora
by
Jain, Manish
,
Mande, Sharmila S.
,
Dubey, Ashok Kumar
in
45/23
,
631/326/2565/2134
,
631/326/2565/2142
2019
Fructo-oligosaccharides (FOS), a prebiotic supplement, is known for its Bifidogenic capabilities. However, aspects such as effect of variable quantities of FOS intake on gut microbiota, and temporal dynamics of gut microbiota (transitioning through basal, dosage, and follow-up phases) has not been studied in detail. This study investigated these aspects through a randomized, double-blind, placebo-controlled, dose-response relationship study. The study involved 80 participants being administered FOS at three dose levels (2.5, 5, and 10 g/day) or placebo (Maltodextrin 10 g/day) during dosage phase. Microbial DNA extracted from fecal samples collected at 9 intervening time-points was sequenced and analysed. Results indicate that FOS consumption increased the relative abundance of OTUs belonging to
Bifidobacterium
and
Lactobacillus
. Interestingly, higher FOS dosage appears to promote, in contrast to Maltodextrin, the selective proliferation of OTUs belonging to
Lactobacillus
. While consumption of prebiotics increased bacterial diversity, withdrawal led to its reduction. Apart from probiotic bacteria, a significant change was also observed in certain butyrate-producing microbes like
Faecalibacterium
,
Ruminococcus
and
Oscillospira
. The positive impact of FOS on butyrate-producing bacteria and FOS-mediated increased bacterial diversity reinforces the role of prebiotics in conferring beneficial functions to the host.
Journal Article